Learning to Crawl: Determining the Role of Genetic Abnormalities on Postoperative Outcomes in Congenital Heart Disease

Abstract

Background Our cardiac center established a systematic approach for inpatient cardiovascular genetics evaluations of infants with congenital heart disease, including routine chromosomal microarray (CMA) testing. This provides a new opportunity to investigate correlation between genetic abnormalities and postoperative course. Methods and Results Infants who underwent congenital heart disease surgery as neonates (aged ≤28 days) from 2015 to 2020 were identified. Cases with trisomy 21 or 18 were excluded. Diagnostic genetic results or CMA with variant of uncertain significance were considered abnormal. We compared postoperative outcomes following initial congenital heart disease surgery in patients found to have genetic abnormality to those who had negative CMA. Among 355 eligible patients, genetics consultations or CMA were completed in 88%. A genetic abnormality was identified in 73 patients (21%), whereas 221 had negative CMA results. Genetic abnormality was associated with prematurity, extracardiac anomaly, and lower weight at surgery. Operative mortality rate was 9.6% in patients with a genetic abnormality versus 4.1% in patients without an identified genetic abnormality (P=0.080). Mortality was similar when genetic evaluations were diagnostic (9.3%) or identified a variant of uncertain significance on CMA (10.0%). Among 14 patients with 22q11.2 deletion, the 2 mortality cases had additional CMA findings. In patients without extracardiac anomaly, genetic abnormality was independently associated with increased mortality (P=0.019). CMA abnormality was not associated with postoperative length of hospitalization, extracorporeal membrane oxygenation, or >7 days to initial extubation. Conclusions Routine genetic evaluations and CMA may help to stratify mortality risk in severe congenital heart disease with syndromic or nonsyndromic presentations.

Keywords: cardiothoracic surgery; chromosomal microarray; congenital heart disease; copy‐number variants; genetics.

Figure 1. Overview of study population.

Asterisk (*) indicates the 294 patients who were included for the analysis of postoperative outcomes. Genetic abnormality was defined as CNV or genetic diagnosis established by geneticist consultation. CHD indicates congenital heart disease; CMA, chromosomal microarray; CNV, copy‐number variant; and VUS, variant of uncertain significance.

Figure 2. Results of multivariate analysis for characteristics associated with operative mortality among neonates without extracardiac anomaly.

Log odds ratios depicted on the x axis are estimated through multivariate logistic regression model. CHD indicates congenital heart disease; and STAT, Society of Thoracic Surgeons‐European Association for Cardio‐Thoracic Surgery.